Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance.

Abstract:

:Insulin and insulin-like growth factor 1 (IGF1) are ubiquitous growth factors that regulate proliferation in most mammalian tissues including pancreatic islets. To explore the specificity of insulin receptors in compensatory beta-cell growth, we examined two models of insulin resistance. In the first model, we used liver-specific insulin receptor knockout (LIRKO) mice, which exhibit hyperinsulinemia without developing diabetes due to a compensatory increase in beta-cell mass. LIRKO mice, also lacking functional insulin receptors in beta-cells (beta IRKO/LIRKO), exhibited severe glucose intolerance but failed to develop compensatory islet hyperplasia, together leading to early death. In the second model, we examined the relative significance of insulin versus IGF1 receptors in islet growth by feeding high-fat diets to beta IRKO and beta-cell-specific IGF1 receptor knockout (beta IGFRKO) mice. Although both groups on the high-fat diet developed insulin resistance, beta IRKO, but not beta IGFRKO, mice exhibited poor islet growth consistent with insulin-stimulated phosphorylation, nuclear exclusion of FoxO1, and reduced expression of Pdx-1. Together these data provide direct genetic evidence that insulin/FoxO1/Pdx-1 signaling is one pathway that is crucial for islet compensatory growth response to insulin resistance.

authors

Okada T,Liew CW,Hu J,Hinault C,Michael MD,Krtzfeldt J,Yin C,Holzenberger M,Stoffel M,Kulkarni RN

doi

10.1073/pnas.0608703104

subject

Has Abstract

pub_date

2007-05-22 00:00:00

pages

8977-82

issue

21

eissn

0027-8424

issn

1091-6490

pii

0608703104

journal_volume

104

pub_type

杂志文章
  • Functional redundancy of worm spliceosomal proteins U1A and U2B''.

    abstract::In Caenorhabditis elegans, the small nuclear ribonucleoprotein (snRNP)-associated proteins U1A and U2B'' are approximately 50% identical to each other, and neither bears signature characteristics of mammalian U1A or U2B'' or the single Drosophila homolog, SNF. We show here that the genes that encode these proteins (rn...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0701720104

    authors: Saldi T,Wilusz C,MacMorris M,Blumenthal T

    更新日期:2007-06-05 00:00:00

  • Characterization of a cDNA coding for human factor VII.

    abstract::Factor VII is a precursor to a serine protease that is present in mammalian plasma. In its activated form, it participates in blood coagulation by activating factor X and/or factor IX in the presence of tissue factor and calcium. Clones coding for factor VII were obtained from two cDNA libraries prepared from poly(A) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.8.2412

    authors: Hagen FS,Gray CL,O'Hara P,Grant FJ,Saari GC,Woodbury RG,Hart CE,Insley M,Kisiel W,Kurachi K

    更新日期:1986-04-01 00:00:00

  • Visualizing the formation of the Kondo lattice and the hidden order in URu(2)Si(2).

    abstract::Heavy electronic states originating from the f atomic orbitals underlie a rich variety of quantum phases of matter. We use atomic scale imaging and spectroscopy with the scanning tunneling microscope to examine the novel electronic states that emerge from the uranium f states in URu(2)Si(2). We find that, as the tempe...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1005892107

    authors: Aynajian P,da Silva Neto EH,Parker CV,Huang Y,Pasupathy A,Mydosh J,Yazdani A

    更新日期:2010-06-08 00:00:00

  • Diverse Toll-like receptors utilize Tpl2 to activate extracellular signal-regulated kinase (ERK) in hemopoietic cells.

    abstract::Engaging mammalian Toll-like receptors (TLRs) activate both the NF-kappaB and mitogen-activated protein kinase signaling pathways. Here we establish that mitogen-activated protein 3 kinase Tpl2, levels of which are markedly reduced in nfkb1(-/-) cells, is required for extracellular signal-regulated kinase (ERK) activa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0511113103

    authors: Banerjee A,Gugasyan R,McMahon M,Gerondakis S

    更新日期:2006-02-28 00:00:00

  • Microbial biomarkers reveal a hydrothermally active landscape at Olduvai Gorge at the dawn of the Acheulean, 1.7 Ma.

    abstract::Landscape-scale reconstructions of ancient environments within the cradle of humanity may reveal insights into the relationship between early hominins and the changing resources around them. Many studies of Olduvai Gorge during Pliocene-Pleistocene times have revealed the presence of precession-driven wet-dry cycles a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2004532117

    authors: Sistiaga A,Husain F,Uribelarrea D,Martín-Perea DM,Ferland T,Freeman KH,Diez-Martín F,Baquedano E,Mabulla A,Domínguez-Rodrigo M,Summons RE

    更新日期:2020-10-06 00:00:00

  • Purification and characterization of the retina-specific cell-aggregating factor.

    abstract::The tissue-specific, cell-aggregating component of embryonic neural retina cells was purified from the retina cell-aggregating factor and characterized as a glycoprotein. Its molecular weight in solution is in the range of 50,000, and it contains 10-15% carbohydrate. The amino-acid and carbohydrate compositions have b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.3.916

    authors: Hausman RE,Moscona AA

    更新日期:1975-03-01 00:00:00

  • Orthogonal arrangement of rhythm-generating microcircuits in the hippocampus.

    abstract::As a structure involved in learning and memory, the hippocampus functions as a network. The functional differentiation along the longitudinal axis of the hippocampus is poorly demarcated in comparison with the transverse axis. Using patch clamp recordings in conjunction with post hoc anatomy, we have examined the patt...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0506259102

    authors: Gloveli T,Dugladze T,Rotstein HG,Traub RD,Monyer H,Heinemann U,Whittington MA,Kopell NJ

    更新日期:2005-09-13 00:00:00

  • Aging and resistance to oxidative damage in Caenorhabditis elegans.

    abstract::The dauer larva state and the age-1 mutation, both of which extend life-span in Caenorhabditis elegans, were tested for hyperresistance to cellular damage that may be relevant to aging. The age-1 strain TJ401 displayed hyperresistance to oxidative stress relative to its parental strain. The activities of two enzymes t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.19.8905

    authors: Larsen PL

    更新日期:1993-10-01 00:00:00

  • PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence.

    abstract::Drug discovery in psychiatry has been limited to chemical modifications of compounds originally discovered serendipitously. Therefore, more mechanism-oriented strategies of drug discovery for mental disorders are awaited. Schizophrenia is a devastating mental disorder with synaptic disconnectivity involved in its path...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1321109111

    authors: Hayashi-Takagi A,Araki Y,Nakamura M,Vollrath B,Duron SG,Yan Z,Kasai H,Huganir RL,Campbell DA,Sawa A

    更新日期:2014-04-29 00:00:00

  • Perilipin ablation results in a lean mouse with aberrant adipocyte lipolysis, enhanced leptin production, and resistance to diet-induced obesity.

    abstract::Perilipin coats the lipid droplets of adipocytes and is thought to have a role in regulating triacylglycerol hydrolysis. To study the role of perilipin in vivo, we have created a perilipin knockout mouse. Perilipin null (peri(-/-)) and wild-type (peri(+/+)) mice consume equal amounts of food, but the adipose tissue ma...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.101042998

    authors: Tansey JT,Sztalryd C,Gruia-Gray J,Roush DL,Zee JV,Gavrilova O,Reitman ML,Deng CX,Li C,Kimmel AR,Londos C

    更新日期:2001-05-22 00:00:00

  • Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system.

    abstract::We have previously shown that the G protein of vesicular stomatitis virus (VSV-G) can be incorporated into the virions of retroviruses. Since expression of VSV-G is toxic to most mammalian cells, development of stable VSV-G packaging cell lines requires inducible VSV-G expression. We have modified the tetracycline-ind...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.19.10057

    authors: Chen ST,Iida A,Guo L,Friedmann T,Yee JK

    更新日期:1996-09-17 00:00:00

  • Nitrosopumilus maritimus genome reveals unique mechanisms for nitrification and autotrophy in globally distributed marine crenarchaea.

    abstract::Ammonia-oxidizing archaea are ubiquitous in marine and terrestrial environments and now thought to be significant contributors to carbon and nitrogen cycling. The isolation of Candidatus "Nitrosopumilus maritimus" strain SCM1 provided the opportunity for linking its chemolithotrophic physiology with a genomic inventor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0913533107

    authors: Walker CB,de la Torre JR,Klotz MG,Urakawa H,Pinel N,Arp DJ,Brochier-Armanet C,Chain PS,Chan PP,Gollabgir A,Hemp J,Hügler M,Karr EA,Könneke M,Shin M,Lawton TJ,Lowe T,Martens-Habbena W,Sayavedra-Soto LA,Lang D,Sieve

    更新日期:2010-05-11 00:00:00

  • Vacuolar H(+)-pumping ATPase variable transport coupling ratio controlled by pH.

    abstract::The eukaryote endomembrane system contains a class of H(+)-pumping ATPase (H(+)-ATPases) of the vacuolar type (V-ATPases) that are responsible for the acidification of organelles. Their action is critical to numerous physiological processes, but the regulatory mechanisms that may control activity are not yet fully und...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.18.8547

    authors: Davies JM,Hunt I,Sanders D

    更新日期:1994-08-30 00:00:00

  • The compression hypothesis and temporal resource partitioning.

    abstract::Contingency models of feeding compare the energy per unit time gained from utilizing a resource unit of a particular kind (food types, habitat patches, time periods) against that energy/time expected if the unit is skipped. Optimally, an animal should reject the particular unit if and only if the former energy/time is...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.10.4169

    authors: Schoener TW

    更新日期:1974-10-01 00:00:00

  • Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.

    abstract::Age-related macular degeneration (AMD) is the most common cause of blindness for individuals age 50 and above in the developed world. Abnormal growth of choroidal blood vessels, or choroidal neovascularization (CNV), is a hallmark of the neovascular (wet) form of advanced AMD and leads to significant vision loss. A gr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1620898114

    authors: Hasegawa E,Inafuku S,Mulki L,Okunuki Y,Yanai R,Smith KE,Kim CB,Klokman G,Bielenberg DR,Puli N,Falck JR,Husain D,Miller JW,Edin ML,Zeldin DC,Lee KSS,Hammock BD,Schunck WH,Connor KM

    更新日期:2017-09-05 00:00:00

  • Compression of the DNA substrate by a viral packaging motor is supported by removal of intercalating dye during translocation.

    abstract::Viral genome packaging into capsids is powered by high-force-generating motor proteins. In the presence of all packaging components, ATP-powered translocation in vitro expels all detectable tightly bound YOYO-1 dye from packaged short dsDNA substrates and removes all aminoacridine dye from packaged genomic DNA in vivo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1214318109

    authors: Dixit AB,Ray K,Black LW

    更新日期:2012-12-11 00:00:00

  • The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting.

    abstract::Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-media...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1533295100

    authors: Fingerle-Rowson G,Petrenko O,Metz CN,Forsthuber TG,Mitchell R,Huss R,Moll U,Müller W,Bucala R

    更新日期:2003-08-05 00:00:00

  • Intrinsic evolutionary constraints on protease structure, enzyme acylation, and the identity of the catalytic triad.

    abstract::The study of proteolysis lies at the heart of our understanding of biocatalysis, enzyme evolution, and drug development. To understand the degree of natural variation in protease active sites, we systematically evaluated simple active site features from all serine, cysteine and threonine proteases of independent linea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1221050110

    authors: Buller AR,Townsend CA

    更新日期:2013-02-19 00:00:00

  • Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability.

    abstract::The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes,...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1718285115

    authors: Smith AS,Nowak RB,Zhou S,Giannetto M,Gokhin DS,Papoin J,Ghiran IC,Blanc L,Wan J,Fowler VM

    更新日期:2018-05-08 00:00:00

  • Increasing crop heterogeneity enhances multitrophic diversity across agricultural regions.

    abstract::Agricultural landscape homogenization has detrimental effects on biodiversity and key ecosystem services. Increasing agricultural landscape heterogeneity by increasing seminatural cover can help to mitigate biodiversity loss. However, the amount of seminatural cover is generally low and difficult to increase in many i...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1906419116

    authors: Sirami C,Gross N,Baillod AB,Bertrand C,Carrié R,Hass A,Henckel L,Miguet P,Vuillot C,Alignier A,Girard J,Batáry P,Clough Y,Violle C,Giralt D,Bota G,Badenhausser I,Lefebvre G,Gauffre B,Vialatte A,Calatayud F,Gil-T

    更新日期:2019-08-13 00:00:00

  • Evolutionary conservation of the insulinoma gene rig and its possible function.

    abstract::We have identified a gene, rig (rat insulinoma gene), that is activated in chemically induced rat insulinomas but not in normal pancreatic islets or in regenerating islets. In the present study, we have found that the insulinoma gene was activated in a BK virus-induced hamster insulinoma cell line and in a spontaneous...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.19.6659

    authors: Inoue C,Shiga K,Takasawa S,Kitagawa M,Yamamoto H,Okamoto H

    更新日期:1987-10-01 00:00:00

  • A model system to study genomic imprinting of human genes.

    abstract::Somatic-cell hybrids have been shown to maintain the correct epigenetic chromatin states to study developmental globin gene expression as well as gene expression on the active and inactive X chromosomes. This suggests the potential use of somatic-cell hybrids containing either a maternal or a paternal human chromosome...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.25.14857

    authors: Gabriel JM,Higgins MJ,Gebuhr TC,Shows TB,Saitoh S,Nicholls RD

    更新日期:1998-12-08 00:00:00

  • Proteins of Escherichia coli come in sizes that are multiples of 14 kDa: domain concepts and evolutionary implications.

    abstract::Initial attempts to correlate the distribution of gene density (number of gene loci per unit length on the linkage map) with the distribution of lengths of coding sequences have led to the observation that 46% of approximately 1000 sampled proteins in Escherichia coli have molecular masses of n X 14,000 +/- 2500 dalto...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.5.1198

    authors: Savageau MA

    更新日期:1986-03-01 00:00:00

  • Conformational changes of calmodulin upon Ca2+ binding studied with a microfluidic mixer.

    abstract::A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton micros...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0710810105

    authors: Park HY,Kim SA,Korlach J,Rhoades E,Kwok LW,Zipfel WR,Waxham MN,Webb WW,Pollack L

    更新日期:2008-01-15 00:00:00

  • Membrane-bound MinDE complex acts as a toggle switch that drives Min oscillation coupled to cytoplasmic depletion of MinD.

    abstract::The Escherichia coli Min system self-organizes into a cell-pole to cell-pole oscillator on the membrane to prevent divisions at the cell poles. Reconstituting the Min system on a lipid bilayer has contributed to elucidating the oscillatory mechanism. However, previous in vitro patterns were attained with protein densi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1600644113

    authors: Vecchiarelli AG,Li M,Mizuuchi M,Hwang LC,Seol Y,Neuman KC,Mizuuchi K

    更新日期:2016-03-15 00:00:00

  • The C-terminal domain-phosphorylated IIO form of RNA polymerase II is associated with the transcription repressor NC2 (Dr1/DRAP1) and is required for transcription activation in human nuclear extracts.

    abstract::Activation of class II gene transcription may involve alleviation of transcription repression as well as stimulation of the assembly and function of the general RNA polymerase (RNAP) II transcription machinery. Here, we investigated whether activator-reversible transcription repression by NC2 (Dr1/DRAP1) contributes t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.140202297

    authors: Castaño E,Gross P,Wang Z,Roeder RG,Oelgeschläger T

    更新日期:2000-06-20 00:00:00

  • The neural basis of language development: Changes in lateralization over age.

    abstract::We have long known that language is lateralized to the left hemisphere (LH) in most neurologically healthy adults. In contrast, findings on lateralization of function during development are more complex. As in adults, anatomical, electrophysiological, and neuroimaging studies in infants and children indicate LH latera...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1905590117

    authors: Olulade OA,Seydell-Greenwald A,Chambers CE,Turkeltaub PE,Dromerick AW,Berl MM,Gaillard WD,Newport EL

    更新日期:2020-09-22 00:00:00

  • Deconstruction of biomass enabled by local demixing of cosolvents at cellulose and lignin surfaces.

    abstract::A particularly promising approach to deconstructing and fractionating lignocellulosic biomass to produce green renewable fuels and high-value chemicals pretreats the biomass with organic solvents in aqueous solution. Here, neutron scattering and molecular-dynamics simulations reveal the temperature-dependent morpholog...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1922883117

    authors: Pingali SV,Smith MD,Liu SH,Rawal TB,Pu Y,Shah R,Evans BR,Urban VS,Davison BH,Cai CM,Ragauskas AJ,O'Neill HM,Smith JC,Petridis L

    更新日期:2020-07-21 00:00:00

  • Interactive computer surface graphics approach to study of the active site of bovine trypsin.

    abstract::A descriptive medium for the presentation of protein structure has been developed and used to evaluate the structure of the active site of bovine trypsin (EC 3.4.21.4). This technique, involving advanced computer graphics technology, permits the facile display of a representation of the molecular surface of proteins o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.75.11.5409

    authors: Feldmann RJ,Bing DH,Furie BC,Furie B

    更新日期:1978-11-01 00:00:00

  • Dopa decarboxylase activity of the living human brain.

    abstract::Monoaminergic neurons use dopa decarboxylase (DDC; aromatic-L-amino-acid carboxy-lyase, EC 4.1.1.28) to form dopamine from L-3,4-dihydroxyphenylalanine (L-dopa). We measured regional dopa decarboxylase activity in brains of six healthy volunteers with 6-[18F]fluoro-L-dopa and positron emission tomography. We calculate...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.7.2721

    authors: Gjedde A,Reith J,Dyve S,Léger G,Guttman M,Diksic M,Evans A,Kuwabara H

    更新日期:1991-04-01 00:00:00